Causal association between systemic diseases and periodontitis: a two-way two-sample Mendelian randomization study

The aim of the present study was to conduct bidirectional two-sample Mendelian randomization (MR) to explore causality between systemic diseases and periodontitis amid confounding factors.

Genome-wide association study (GWAS) summary statistics were obtained from the IEU OpenGWAS project, FinnGen consortium, and GLIDE consortium. The exposures included a range of systemic diseases, such as diabetic ketoacidosis, coronary heart disease, myocardial infarction, stroke, coronary atherosclerosis, diabetic nephropathy, diabetic neuropathy, diabetic retinopathy, cataracts, nonalcoholic fatty liver disease, osteoporosis, and cardiac arrhythmia, and the outcomes were periodontitis and chronic periodontitis. The primary analytical method was inverse-variance weighted (IVW) MR, complemented by MR-Egger, weighted median, and weighted mode methods. Sensitivity analyses, including MR-PRESSO, MR-Egger intercept test, and Cochran's Q test, were performed to assess the robustness of the findings.

In the forward MR analysis, no significant evidence was found to support a causal effect of genetic liability to the selected systemic diseases on the risk of periodontitis or chronic periodontitis (all P > .05). In the reverse MR analysis, a genetically predicted causal relationship was identified, suggesting that periodontitis is a risk factor for osteoporosis (IVW, OR 1.16, 95% CI 1.01-1.33, P = .031). No other significant causal effects of periodontitis on the other studied diseases were found. Sensitivity analyses did not detect significant horizontal pleiotropy for the positive finding.

Novel evidence is provided suggesting that periodontitis may causally increase the risk of osteoporosis. These findings highlight the systemic impact of oral health and suggest that preventing and treating periodontitis could be a potential strategy in osteoporosis management. Clinically, integrating periodontal screening into the risk assessment protocols for patients susceptible to osteoporosis may optimize early intervention and multidisciplinary patient management.